miR-155预测乳腺癌侵袭及预后的研究

Correlation of miR-155 on formalin-fixed paraffin embedded tissues with invasiveness and prognosis of breast cancer

目的探讨miR-155在乳腺癌侵袭中的作用及其作为乳腺癌预后预测新指标的可能性。方法88例乳腺癌患者于2002年3月至2005年12月接受改良根治术，随访资料完整。采用real—timePCR对原发肿瘤蜡块进行miR-155表达水平的测定，配对t检验比较癌组织和癌旁正常组织中miR-155的水平差异，MannWhitney—U非参数检验比较miR-155表达水平和乳腺癌临床病理参数的关系，预后分析采用Kaplan—Meier生存分析和Log—rank检验，采用Cox回归进行单因素及多因素分析。结果相比癌旁正常组织，癌组织中miR．155表达明显上调（t=6．75，P=0．000），在淋巴结转移、肿瘤较大、分期晚、HER．2阳性及伴有脉管瘤栓的乳腺癌组织中miR-155表达水平较高（Z=-6．320～-2．041，P=0．000～0．041）。以中位值2-ACt：4．87为截断值，Kaplan—Meier生存分析表明，低miR-155表达者总生存率高于miR-155高表达者（X^2=6．396，P=0．011）。单因素及多因素分析显示，miR-155表达与总生存率相关（HR=1．58，95％CI：0．87～3．16，P=0．082）。结论miR-155与淋巴结转移、肿瘤大小及HER-2基因表达显著相关，可作为乳腺癌侵袭潜能的预测指标。

Objective To investigate the potential use of miR-155 as novel breast cancer biomarker. Methods There were 88 breast cancer patients underwent modified mastectomy and had detailed clinical follow-up information. Extracting RNA from the formalin-fixed paraffin embedded （FFPE） samples, miR-155 levels were quantified by real-time-PCR, miR-155 levels among clinico-pathological variables were accessed by Mann Whitney-U test. Overall survival curve was derived from Kaplan-Meier estimates and the curve was compared by Log-rank test. Cox regression analysis was used for multivariate analysis. All statistical tests were two-sided. Results Significantly higher miR-155 level was found in tumor tissue compared to paired normal tissue （t = 6. 75, P = 0. 000）. A potential relationship between miR-155 levels and existing clinico-pathological parameters of breast cancer, such as menstrual status, tumor size, nodal involvement, stage of disease, hormone receptor status, HER-2 status, histological grade or tumor subtype was investigated. Up-regulated miR-155 level was observed in breast cancer with lymph node metastasis, pT3 ＋ 4, advanced TNM stage, HER-2 positive and with vascular invasion （ Z = - 6. 320 to - 2. 041, P = 0. 000 to 0. 041 ）. When considering 2 ^- △Ct, = 4. 87 （ median level） as cut-off value, patients with miR-155 up-regulation showed a positive association towards a shorter overall survival （ X^2 = 6. 396, P =0. 011）. In Cox multivariate analysis, miR-155 expression on FFPE was shown an inverse trend for outcomes of breast cancer （HR = 1.58, 95% CI：0. 87-3. 16, P = 0. 082）. Conclusions miR-155, as an oncomir, promotes lymph node involvement and vascular invasion and accompanies over-expressed HER-2 on breast cancer FFPE tissue. It suggests that miR-155 could predict the invasiveness.